Tumor suppressive effect of PARP1 and FOXO3A in gastric cancers and its clinical implications
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See-Hyoung Park1,2,*, Kyu Yun Jang4,*, Min Jae Kim1,3,*, Sarah Yoon1, Yuna Jo1,3, So Mee Kwon1,3, Kyoung Min Kim4, Keun Sang Kwon5, Chan Young Kim6, Hyun Goo Woo1,3
1Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea
2Program in Nano Science and Technology, Department of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Suwon, Republic of Korea
3Department of Biomedical Sciences, Graduate School, Ajou University, Suwon, Republic of Korea
4Department of Pathology, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju, Republic of Korea
5Department of Preventive Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea
6Department of Surgery, Chonbuk National University Medical School, Jeonju, Republic of Korea
*These authors have contributed equally to this work
Hyun Goo Woo, e-mail: email@example.com
Keywords: olaparib, PARP1, FOXO3A, prognosis, G2/M arrest
Received: May 27, 2015 Accepted: October 22, 2015 Published: November 02, 2015
Poly (ADP-ribose) polymerase1 (PARP1) has been reported as a possible target for chemotherapy in many cancer types. However, its action mechanisms and clinical implications for gastric cancer survival are not yet fully understood. Here, we investigated the effect of PARP1 inhibition in the growth of gastric cancer cells. PARP1 inhibition by Olaparib or PARP1 siRNA could significantly attenuate growth and colony formation of gastric cancer cells, and which were mediated through induction of G2/M cell cycle arrest but not apoptosis. FOXO3A expression was induced by PARP1 inhibition, suggesting that FOXO3A might be one of downstream target of the PARP1 effect on gastric cancer cell growth. In addition, by performing tissue microarrays on the 166 cases of gastric cancer patients, we could observe that the expression status of PARP1 and FOXO3A were significantly associated with overall survival (OS) and relapse-free survival (RFS). Strikingly, combined expression status of PARP1 and FOXO3A showed better prediction for patient’s clinical outcomes. The patient group with PARP1+/FOXO3A− expression had the worst prognosis while the patient group with PARP1−/FOXO3A+ had the most favorable prognosis (OS: P = 6.0 × 10−9, RFS: P = 2.2 × 10−8). In conclusion, we suggest that PARP1 and FOXO3A play critical roles in gastric cancer progression, and might have therapeutic and/or diagnostic potential in clinic.
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